THE ROLE OF GLUTAMATE REUPTAKE IN REGULATION OF GLUTAMATE RESPONSES IN APLYSIA NEURONS

Glutamate elicits several different responses on neurons of isolated g anglia of Aplysia, the most common of which is a hyperpolarization due to conductance increases to either chloride or potassium. We have inv estigated the actions of aspartate and cysteate on the responses to gl utamate. Neither aspartate nor cysteate is potent in activation of glu tamate receptors. However both aspartate and cysteate cause a dramatic increase in the response to glutamate when ionophoretically applied b efore the glutamate application. This potentiating effect of aspartate and cysteate is a result of competition with glutamate for the glutam ate transport system, since the potentiation is blocked by coaling and by perfusion with sodium-free sea water. Blockade of glutamate re-upt ake by perfusion of sodium-free sea cater also causes a significant in crease in the response to ionophoretically applied glutamate, which in same neurons may be very large. These results demonstrate that the gl utamate reuptake system has an important role in regulation of the res ponses to glutamate which is similar to that of acetylcholinesterase i n regulation of responses to acetylcholine. These observations may be of particular importance in mammalian systems where excess glutamate i s associated with neuronal excitotoxicity and cell death.